To identify genetic alterations present in Merkel cell carcinoma, we have conducted molecular analyses of human tumors across multiple genome-wide platforms to assay gene expression, identify gene mutations and characterize chromosomal alterations. These date are presently being analyzed to identify key driver alterations for this tumor. We have also begun to generate mice where oncogenic modifications are carried out in specific skin lineages in an attempt to transform Merkel cells in vivo. Finally we have begun work generating new cell lines for Merkel cell carcinoma and are conducting a genetic knock-down screen to identify druggable pathways important for tumor survival.